Cinchona alkaloid salts are known phase transfer catalysts useful in the asymmetric formation of carbon-carbon, carbon-heteroatom or carbon-halide bonds. See Takashi Ooi and Keiji Maruoka, Recent Advances in Asymmetric Phase-Transfer Catalysis, Angew. Chem. Int. Ed. 2007, 46, 4222-4266 (“Maruoka”). Maruoka reviews the various reactions in which phase-transfer catalysis is useful, including enantioselective alkylation, Michael addition, aldol and related reactions and Darzens reaction. Maruoka at page 4223 discusses the advantages of such phase transfer catalysis processes as involving “simple experimental procedures, mild reaction conditions, inexpensive and environmentally benign reagents and solvents and the possibility of conducting large-scale preparations.” Thus, asymmetric phase transfer catalysis remains an important area for organic chemistry research.
The present invention is directed to novel bis-quarternary cinchona alkaloid salts and the use of bis-quarternary cinchona alkaloid salts in asymmetric phase transfer catalysis. On certain substrates and under specific reaction conditions, the inventors have discovered that the use of bis-quarternary cinchona alkaloid salts in asymmetric phase transfer catalysis surprisingly provides for a more active and efficient process as compared to mono-quarternary catalysts, providing high efficiency rates and asymmetric products in high enantiomeric excess.